The cytochalasins are a group of cytotoxic fungal metabolites which exhibit a complex array of biological activities. These molecules have been used extensively as probes of cell biological processes. The specific objectives of our investigation are: (1)\the design and synthesis of simplified cytochalasin analogs into which [unreadable]13[unreadable]C-labels, fluorophores, affinity labeling functionality, and/or modified functional groups have been incorporated; (2)\the determination of specific structure-activity correlations of simplified cytochalasins; (3)\determination of the specific molecular aspects of actin polymerization; and (4)\identification and characterization of cellular cytochalasin receptors. Efficient synthetic strategies have been developed to prepare functionally versatile perhydroisoindolones from which simplified cytochalasin derivatives are being prepared. One of these simplified derivatives, lacking the C-7 OH and the large ring retains ca. 50 percent of the actin assembly inhibition activity of cytochalasin D. It is anticipated that subsequently synthesized analogs will exhibit a more well-defined spectrum of biological activities, enabling delineation of specific molecular events involved with membrane and cytoskeletal processes. (L)